title: Novel bis-ortho-alkoxy-para-piperazinesubstituted-2,4-dianilinopyrimidines (KRCA-0008) as potent and selective ALK inhibitors for anticancer treatment.
abstract: The synthesis of bis-ortho-alkoxy-para-piperazinesubstituted-2,4-dianilinopyrimidines is described and their structure-activity-relationship to anaplastic lymphoma kinase (ALK) is presented. KRCA-0008 is selective and potent to ALK and Ack1, and displays drug-like properties without hERG liability. KRCA-0008 demonstrates in vivo efficacy comparable to Crizotinib in xenograft mice model.
authors.affiliation: Bio-Organic Science Division, Korea Research Institute of Chemical Technology, PO Box 107, Daejeon 305-600, Republic of Korea.
authors.forename: Chi Hoon
authors.initials: CH
authors.lastname: Park
authors.forename: Hyeonjeong
authors.initials: H
authors.lastname: Choe
authors.forename: In-Young
authors.initials: IY
authors.lastname: Jang
authors.forename: So Yeong
authors.initials: SY
authors.lastname: Kwon
authors.forename: Muhammad
authors.initials: M
authors.lastname: Latif
authors.forename: Heung Kyoung
authors.initials: HK
authors.lastname: Lee
authors.forename: Hyeon Ji
authors.initials: HJ
authors.lastname: Lee
authors.forename: Eun Hye
authors.initials: EH
authors.lastname: Yang
authors.forename: Jeong In
authors.initials: JI
authors.lastname: Yun
authors.forename: Chong Hak
authors.initials: CH
authors.lastname: Chae
authors.forename: Sung Yun
authors.initials: SY
authors.lastname: Cho
authors.forename: Sang Un
authors.initials: SU
authors.lastname: Choi
authors.forename: Jae Du
authors.initials: JD
authors.lastname: Ha
authors.forename: Heejung
authors.initials: H
authors.lastname: Jung
authors.forename: Hyoung Rae
authors.initials: HR
authors.lastname: Kim
authors.forename: Pilho
authors.initials: P
authors.lastname: Kim
authors.forename: Chong Ock
authors.initials: CO
authors.lastname: Lee
authors.forename: Chang-Soo
authors.initials: CS
authors.lastname: Yun
authors.forename: Kwangho
authors.initials: K
authors.lastname: Lee
mesh_terms: D000077548:Anaplastic Lymphoma Kinase; D000818:Animals; D045744:Cell Line, Tumor; D000077547:Crizotinib; D004195:Disease Models, Animal; D008175:Lung Neoplasms / Q000188:drug therapy; D051379:Mice; D010879:Piperazines / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D011720:Pyrazoles / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D011743:Pyrimidines / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D023041:Xenograft Model Antitumor Assays
chemical_list: D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011725:Pyridines; D011743:Pyrimidines; D000077547:Crizotinib; C000626174:Alk protein, mouse; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases
keywords: ACK1; ALK; Diaminopyrimidine; Inhibitors; Kinases; N-Acetylpiperidine; NSCLC